Influvac Tetra: clinical experience on safety, efficacy, and immunogenicity

ABSTRACT

Introduction

This paper summarizes the safety and immunogenicity data of Influvac Tetra across all age groups starting from 6 months of age, obtained during its clinical development program.

Areas covered

The article covers the clinical development program of Influvac Tetra based on five registration studies that included different age groups, different comparators, and participants from Europe and Asia. Safety and immunogenicity were assessed in all studies and in one study, the efficacy of Influvac Tetra was assessed.

Expert opinion

Seasonal influenza is a vaccine-preventable disease that can cause serious complications. Several types of influenza vaccines are available, including egg-based (standard dose, high dose, and adjuvanted), cell-based, and recombinant. The COVID-19 pandemic has stimulated innovation in the development such as mRNA vaccines. However, these vaccines are still in development and the true value still has to be proven. Regardless of the type of vaccine, it is also important to increase overall vaccination coverage. ECDC recommends that EU Member States implement action plans and policies aimed at reaching 75% coverage in at-risk groups and healthcare workers. Even so, vaccine coverage is still far from recommended.

KEYWORDS:

• Influvac Tetra
• subunit vaccine
• safety
• reactogenicity
• immunogenicity
• tetravalent
• egg-based vaccine
• influenza

Article highlights

• Trivalent influenza vaccines (TIVs) contain two A-strains (H1N1 and H3N2) and only one B-strain lineage, thus providing little or limited protection against disease caused by the other B-strain lineage.

• Quadrivalent influenza vaccines (QIVs) contain two A-strains (H1N1 and H3N2) and two B-strain lineages (B/Victoria and B/Yamagata) and therefore can increase overall VE in seasons when both lineages co-circulate.

• The clinical development of Influvac Tetra, a QIV, aimed to support an indication for use similar to the existing approved TIV (Influvac), i.e. prophylaxis of influenza, especially in those at increased risk of associated complications.

• The results of two clinical studies with Influvac Tetra showed consistent immunogenicity across age groups, demonstrating non-inferiority for shared strains and superiority to TIV for the alternate lineage influenza B strains.

• At-risk status did not affect post-vaccination anti-HA antibody levels with Influvac Tetra.

• The absolute vaccine efficacy of Influvac Tetra in the prevention of symptomatic influenza against the matching strains in children aged 6-35 months was 68%, and against any circulating seasonal influenza strain was 54%. Subgroup analyses further demonstrated consistent vaccine efficacy estimates among all age groups, including children under the age of 2 years, making a case that Influvac Tetra is a priming vaccine in young children. Vaccine efficacy persisted throughout the season.

• Besides the hemagglutination inhibition (HI) antibody titers, Influvac Tetra also elicits an increase in neuraminidase inhibition (NI) antibody titers and Virus Neutralization titers (VN).

• Cell-mediated immunity assessed across the entire age range demonstrated increased postvaccination CD4+ T cells producing TNF alpha, IFN gamma, and IL2+, suggesting that vaccination with Influvac Tetra activates T helper cells and confirms its role in inducing cell-mediated immunity.

• Influvac Tetra has a positive benefit-risk balance in children (over 6 months of age), adolescents, adults, and the elderly, and its safety profile is in line with the well-established safety profile of Influvac (TIV).

Declaration of interests

J Rogoll, J Nauta, S van de Witte, and A Kondratenko, are employed by Abbott, the company that manufactures Influvac and Influvac Tetra. S Hadigal and L Colombo are employees of Viatris. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript discloses that they are an owner of intellectual property pertaining to the molecular clamp vaccine platform. They are also a scientific advisor to Vicebio Ltd. A second reviewer has disclosed that they receive honoraria from Abbott. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Author contributions

Laura Colombo, Sanjay Hadigal, Jutta Rogoll and Serge van de Witte contributed to the design and implementation, data interpretation, drafting and editing of this review paper. Jos Nauta was the statistical lead and was primarily involved in the clinical study design, statistical analyses, and data interpretation. Alona Kondratenko revised the manuscript critically for important intellectual content. All authors contributed to the data interpretation, development, and review of this manuscript and confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The sponsor also provided a formal review of this manuscript. All authors met ICMJE criteria and all those who fulfilled those criteria are listed as authors. All authors had access to the study data and made the final decision about where to publish these data and approved submission to this journal.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was funded by Viatris.